When we have medical problems we want to know why. We want a diagnosis and a reason for the diagnosis. But getting a diagnosis is often the start of our questions, not the end. Once we have a diagnosis we immediately ask about the prognosis. What does the diagnosis mean for us today, tomorrow, in 10 years time?
How well is genetic medicine doing answering questions about prognosis?
Genetic diagnosis transformed
The current era of genetic medicine has seen a transformation in genetic diagnosis. We can now make many more diagnoses in many more people. Cheap, fast DNA sequencing has been the foundation of this transformation. Genetic research can now be done on a much larger scale and in many more conditions. This has led to the discovery of hundreds of new disease genes over the last few years.
Genetic testing in the clinic has also been transformed. We now have the capacity and resources to use genetic testing as a first-line diagnostic tool, rather than a luxury commodity to be used sparingly. And we can now test all 20,000 genes in one go, rather than painstakingly and expensively going through individual candidate genes one by one.
Diagnosis is not enough
These amazing advances have had huge benefits for patients, medicine and science. But we must not rest on our laurels. Ending a patients ‘diagnostic odyssey’ is not the true end goal of genetic testing. It is the end of the beginning of the patient journey. And the beginning of a much longer journey of adapting to, living with, managing and treating a condition that may have implications for their entire lives, and for their children’s lives. So, although we can feel proud of the work we have done to increase testing and diagnosis, we must focus attention on the many new questions about prognosis that our successes are generating.
We provide little prognosis informationOne of the most challenging aspects of genetic medicine today, for patients and doctors, is the limited prognosis information we can provide. We can give general estimated information about how a genetic condition affects people on average, but not an individual, personalised road map.
This is particularly difficult when the range of possible impacts and outcomes is very broad. For example, one child with Sotos syndrome due to a specific NSD1 variant may simply have a mild learning disability, whereas a different child with exactly the same NSD1 variant may have a heart defect, debilitating curvature of the spine and limited speech.
We do not know why genetic conditions are so variable
The extraordinary variability in how genetic variants affect different people is one of the reasons we find it so hard to provide good information about prognosis. What is the cause of this variability? Why are people with the same gene mutation affected so differently by it? We don’t know. And we are not close to understanding it. Complex combinations of factors must be involved. Perhaps these overlap with the factors that make us similar, but also very different from our siblings. Chance may well play a part. It is one of the major enigmas in genetics today, and causes many challenges.
We are not collecting enough data on prognosis
Collecting more data is always a good starting point when you are trying to understand something. We have become much better at pulling together the information we need to diagnose and treat people. We are also getting better at collecting and sharing genetic data, driven by the universal recognition that this is essential for variant interpretation. But we are not collecting data on how genetic conditions affect people through their lifetimes. We need to do this routinely, systematically and exhaustively. The medical literature is full of reports of patients that have been severely or unusually affected by a gene variant. These are interesting and valuable. But we also need details of typical patients, so we can build a true picture of how genetic conditions affect people.
Collecting details of how patients are affected by genetic conditions over the years will be very useful. It will make the general information we provide more accurate. And it will be the bedrock on which we start to understand how and why gene variants affect people in the way they do. This will help us become better at giving more personal prognosis information. And, in time, may give us a heads up about what problems are around the corner, and better odds of preventing them.